A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- and Active- Controlled, Treat-Through Study to Evaluate the Efficacy and Safety of Mirikizumab in Patients With Moderately to Severely Active Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,158
- 试验地点
- 571
- 主要终点
- Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Response at Week 52 (Placebo and Mirikizumab)
研究概览
简要总结
The reason for this study is to see if the study drug mirikizumab is safe and effective in participants with moderately to severely active Crohn's disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CD for at least 3 months prior to baseline
- •Confirmed diagnosis of moderate to severe CD as assessed by SF, AP score, and SES-CD
- •Demonstrated intolerance, loss of response or inadequate response to conventional or to biologic therapy for CD
- •If female, subject must meet the contraception recommendations
排除标准
- •Have a current diagnosis of ulcerative colitis, inflammatory bowel disease-unclassified (IBD-U) (formerly known as indeterminate colitis) or short bowel syndrome
- •Currently have or are suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained, adequately treated and resolved at least 3 weeks prior to baseline or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery
- •Have a stoma, ileoanal pouch or ostomy
- •Have had a bowel resection within 6 months, or any kind of intra-abdominal or extra abdominal surgery within 3 months of baseline
- •Have ever received any monoclonal antibodies binding IL-23
研究组 & 干预措施
Placebo
Participants received Placebo intravenously (IV) or subcutaneously (SC) every 4 weeks (Q4W). Any participant in the placebo arm who was considered a non-responder at Week 12 received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W for the remainder of the study. Nonresponse is defined as failing to achieve at least a 30% decrease in stool frequency (SF) and/or abdominal pain (AP) and be no worse than baseline.
干预措施: Placebo (Drug)
300 mg Mirikizumab
Participants received 900 milligrams (mg) Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W
干预措施: Mirikizumab (Drug)
90 mg Ustekinumab
Participants received 6 mg/kg Ustekinumab IV for one dose, then 90 mg SC every 8 weeks (Q8W)
干预措施: Ustekinumab (Drug)
300 mg Mirikizumab (Adolescents)
Participants received open label 900 mg Mirikizumab IV for 3 doses, then 300 mg SC Q4W
干预措施: Mirikizumab (Drug)
结局指标
主要结局
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Response at Week 52 (Placebo and Mirikizumab)
时间窗: Week 12 to Week 52
Clinical response by patient reported outcome (PRO) defined as ≥30% decrease in stool frequency (SF) and/or abdominal pain (AP) \& neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Endoscopic response defined as ≥50% reduction from baseline in total Simple Endoscopic Score for Crohn's Disease (SES-CD) score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence \& size of ulcers (none=0; diameter 0.1-0.5 cm=1; 0.5-2 cm=2; \>2 cm=3); extent of ulcerated surface (none=0; \<10%=1; 10% to 30%=2; \>30%=3); extent of affected surface (none=0; \<50%=1; 50% to 75%=2; \>75%=3); presence \& type of narrowing (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission at Week 52 (Placebo and Mirikizumab)
时间窗: Week 12 to Week 52
Clinical response by PRO defined as ≥ 30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical remission defined as Crohn's Disease Activity Index (CDAI) total score \<150. The CDAI is an 8-item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter \[hematocrit\]).. Total score range of 0 to 600 points.
次要结局
- Percentage of Adult Participants Achieving Endoscopic Response at Week 12 (Placebo and Mirikizumab)(Week 12)
- Percentage of Adult Participants Achieving Endoscopic Response at Week 52(Week 52)
- Percentage of Adult Participants Achieving Clinical Remission at Week 12 (Placebo and Mirikizumab)(Week 12)
- Percentage of Adult Participants Achieving Clinical Remission at Week 52(Week 52)
- Percentage of Adult Participants Achieving Endoscopic Remission at Week 12 (Placebo and Mirikizumab)(Week 12)
- Change From Baseline in Urgency Numeric Rating Scale (NRS) at Week 12 in Adult Participants (Placebo and Mirikizumab)(Baseline, Week 12)
- Change From Baseline in Urgency NRS at Week 52 in Adult Participants (Placebo and Mirikizumab)(Baseline, Week 52)
- Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission by PRO at Week 52 (Placebo and Mirikizumab)(Week 12 to Week 52)
- Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 (Placebo and Mirikizumab)(Week 12 to Week 52)
- Percentage of Adult Participants Achieving Clinical Response at Week 12 and Corticosteroid-free Clinical Remission at Week 52 (Placebo and Mirikizumab)(Week 12 to Week 52)
- Change From Baseline in C-Reactive Protein (CRP) at Week 52 in Adult Participants (Placebo and Mirikizumab)(Baseline, Week 52)
- Change From Baseline in Fecal Calprotectin at Week 52 in Adult Participants (Placebo and Mirikizumab)(Baseline, Week 52)
- Percentage of Adult Participants Achieving Clinical Response at Week 12 and Resolution of Baseline Extraintestinal Manifestations (EIMs) at Week 52 (Placebo and Mirikizumab)(Week 12 to Week 52)
- Percentage of Adult Participants Achieving Clinical Response at Week 12 and ≥50% Reduction in Number of Draining Cutaneous Fistulae at Week 52 in Participants With Draining Cutaneous Fistulae at Baseline (Placebo and Mirikizumab)(Week 12 to Week 52)
- Change From Baseline in Health Related Quality of Life at Week 52 in Adult Participants: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score (Placebo and Mirikizumab)(Baseline, Week 52)
- Adult Population Pharmacokinetics (PopPK): Area Under the Concentration Time Curve (AUC) of Mirikizumab(900 mg Mirikizumab: Week 4: Predose; Week 4, Day 1: Postdose; Week 8, 12: Predose 300 mg Mirikizumab: Week 16, 24, 36: Predose; Week 52)